This application responds to RFA-CA-13-501 which is intended to continue the National Cancer Institute's effort to develop new therapies for adults with high grade gliomas. During the past five years, the ABTC has demonstrated that it is an efficient and capable early phase clinical trial organization able to conduct outstanding science. The ABTC will remain focused on early stage drug development and will use its scientific and clinical trial expertise, patient and laboratory resources, and biospecimens to conduct pharmacokinetic (PK), pharmacodynamic (PD), and imaging studies to characterize drug effects on relevant cellular targets. The consortium has a 20 year history of timely development and activation of multisite pilot and phase I/II brain tumor trials, outstanding data management, and an extensive publication record. It involves talented investigators from multiple disciplines, research nurses, and data managers from 11 brain tumor centers with a proven history of productive relationships with the ABTC Central Operations Office. The ABTC will be led by Drs. Grossman, Nabors, and Wen and a diverse and qualified Consortium Coordinating Committee. The Central Operations Office will be directed by Dr. Grossman and Joy Fisher and Dr. Ye will oversee ABTC's biostatistics. The Clinical Trials Research Program, chaired by Drs. Nabors and Wen, consists of a Research Concept Committee and 10 Discipline Committees (Drug delivery, Immunology, Genomic Profiling, Imaging, Neuropathology, Neurosurgery, PK, PD & Correlative Biology, Preclinical Drug Screening, and Radiation Oncology) chaired by nationally recognized experts. The ABTC has formal mechanisms to dismiss underperforming sites, evaluate new member and guest sites, and review and fund competitive correlative biology research. The ABTC will continue to foster interactions with the NIH, SPOREs, cooperative groups, academic translational research, and industry. An experienced Advisory Panel will provide critical input. The ABTC's goal is to develop more effective therapies by safely and efficiently introducing novel treatment approaches through pilot and phase I/II clinical trials, integrating appropriate PK and PD endpoints into clinical trials, and collaborating with other NCI-funded researchers.